Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/916113

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Title
Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behaviour and blunted corticosterone responses: implications for the double-hit hypothesis
Author/Creator
Walker, Adam K.;  Nakamura, Tamo;  Byrne, Robert J.;  Naicker, Sundresan;  Tynan, Ross J.;  Hunter, Mick;  Hodgson, Deborah M.
Institution
The University of Newcastle. Faculty of Science & Information Technology, School of Psychology
Description
The double-hit hypothesis posits that an early life genetic or environmental insult sets up a neural predisposition to psychopathology, which may emerge in the presence of a subsequent insult, or ‘second hit’ in later life. The current study assessed the effect of neonatal lipopolysaccharide (LPS) exposure on anxiety-like behaviours in the adult Wistar rat. Rats were administered either LPS (Salmonella enterica, serotype enteritidis, 0.05 mg/kg, ip) or saline (equivolume) on days 3 and 5 of life (birth = day 1). In adulthood (85 days), subjects were allocated to either “stress” or “no stress” treatment groups. For the “stress” group, subjects were exposed to a three-day stress protocol consisting of a 30 min period of restraint and isolation. The “no stress” group was left unperturbed but were handled during this period to control for handling effects between adult “stress” and “no stress” conditions. All animals then underwent behavioural testing using standardised tests of anxiety-like behaviour, including either the Hide Box/Open Field, Elevated Plus Maze (EPM) or Acoustic Startle Response (ASR). Time and event measures for restraint and isolation, the Hide Box/Open Field and EPM were recorded using automated tracking software. Startle amplitude and habituation across time was measured in the ASR test. Prior to and following behavioural test sessions, peripheral blood was collected to assess serum corticosterone and ACTH levels. Data analysis indicated that LPS-treated animals exposed to stress in adulthood exhibited increased anxiety-like behaviour across all behavioural tests compared to controls. Sexually dimorphic effects were observed with males exhibiting increased anxiety-related behaviours compared to females (p < .05). Neonatal LPS exposure induced a significant increase in corticosterone compared to controls (p < .05), whereas corticosterone responses to stress in adulthood were associated with a significantly blunted HPA axis response (p < .05). No differences in ACTH were observed. These results lend support to the double-hit hypothesis of anxiety-related behaviour, demonstrating that neonatal immune activation produces an enhanced propensity toward anxiety-related behaviour following stress in adulthood, and that this susceptibility is associated with alterations to HPA axis ontogeny.
Relation
Psychoneuroendocrinology Vol. 34, Issue 10, p. 1515-1525
Publisher Link
http://dx.doi.org/10.1016/j.psyneuen.2009.05.010
Date
2009
Publisher
Elsevier
Keyword(s)
anxiety;  hypothalamic–pituitary–adrenal axis;  neonatal stress;  perinatal programming;  lipopolysaccharide
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/916113
Identifier
ISSN:0306-4530
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Subject
"Psychoneuroendocrinology"
 
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